Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Laboratory of Genome Science, Biosignal Genome Resource Center, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8512, Japan.
Mol Brain. 2021 May 10;14(1):79. doi: 10.1186/s13041-021-00788-5.
Astrocytes are critical regulators of neuronal function in the central nervous system (CNS). We have previously shown that astrocytes in the spinal dorsal horn (SDH) have increased intracellular Ca levels following intraplantar injection of the noxious irritant, formalin. However, the underlying mechanisms remain unknown. We investigated these mechanisms by focusing on the role of descending noradrenergic (NAergic) signaling because our recent study revealed the essential role of the astrocytic Ca responses evoked by intraplantar capsaicin. Using in vivo SDH imaging, we found that the Ca level increase in SDH astrocytes induced by intraplantar formalin injection was suppressed by ablation of SDH-projecting locus coeruleus (LC)-NAergic neurons. Furthermore, the formalin-induced Ca response was dramatically decreased by the loss of α-adrenaline receptors (ARs) in astrocytes located in the superficial laminae of the SDH. Moreover, similar inhibition was observed in mice pretreated intrathecally with an α-AR-specific antagonist. Therefore, activation of α-ARs via descending LC-NAergic signals may be a common mechanism underlying astrocytic Ca responses in the SDH evoked by noxious stimuli, including chemical irritants.
星形胶质细胞是中枢神经系统（CNS）中神经元功能的关键调节者。我们之前已经表明，足底注射有害刺激物福尔马林后，脊髓背角（SDH）中的星形胶质细胞细胞内 Ca 水平升高。然而，其潜在机制仍不清楚。我们通过关注下行去甲肾上腺素能（NAergic）信号的作用来研究这些机制，因为我们最近的研究揭示了足底辣椒素诱发的星形胶质细胞 Ca 反应的重要作用。使用体内 SDH 成像，我们发现足底福尔马林注射引起的 SDH 星形胶质细胞 Ca 水平增加被 SDH 投射蓝斑（LC）-NAergic 神经元消融所抑制。此外，星形胶质细胞中 α-肾上腺素能受体（ARs）的缺失显著降低了福尔马林诱导的 Ca 反应位于 SDH 浅层。此外，鞘内预先给予 α-AR 特异性拮抗剂的小鼠也观察到类似的抑制作用。因此，下行 LC-NAergic 信号通过激活 α-AR 可能是有害刺激物（包括化学刺激物）引起的 SDH 中星形胶质细胞 Ca 反应的共同机制。
